scholarly journals Simultaneous Monitoring of Behavior & Peripheral Clocks in Drosophila Reveals Unstructured Sleep in an Alzheimer's Model

2015 ◽  
Author(s):  
Eleonora Khabirova ◽  
Ko-Fan Chen ◽  
John S O'Neill ◽  
Damian C Crowther
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Biological Clock ◽  
Model Organisms ◽  
Clock Gene Expression ◽  
Biological Phenomena ◽  
Model Of Alzheimer’S Disease ◽  
Sleep Homeostasis ◽  
Regulatory Machinery ◽  
Activity Cycles

Sleep and circadian rhythms are ancient, related biological phenomena controlled by distinct neuronal circuits, whose appropriate regulation is critical for health. Whereas the regulatory machinery underlying sleep homeostasis is ill-defined, the biological clock mechanism is better understood: from cell-intrinsic feedback loops of ‘clock gene’ expression to circuits that facilitate rhythmic behavior. Age- and neurodegeneration related deterioration in sleep/wake timing was first described in humans decades ago, but has only recently been recapitulated in model organisms. In order to delineate the causal relationships between aging, sleep, neuronal function and the molecular clockwork, we have developed FLYGLOW, a broadly applicable bioluminescence-based system which allows rest/activity cycles, sleep consolidation and molecular clock gene expression to be quantified simultaneously in dozens of individual flies over many days/weeks. We show that FLYGLOW outperforms existing methods, and demonstrate the utility of the multiparameter correlational analyses within and between flies that it enables. We go on to show unambiguously that peripheral cellular rhythms can free-run independently of the central pacemakers that drive behavioural cycles. Finally, using a fly model of Alzheimer’s disease (AD) we observe a profound disorganization of sleep and activity cycles, that phenocopies the human disease.

scholarly journals Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure

Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 217
Author(s):  
Chung-Yao Hsu ◽  
Yao-Chung Chuang ◽  
Fang-Chia Chang ◽  
Hung-Yi Chuang ◽  
Terry Ting-Yu Chiou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lead Exposure ◽  
Clock Gene ◽  
Slow Wave Sleep ◽  
Clock Genes ◽  
Negative Impact ◽  
Dark Period ◽  
Clock Gene Expression ◽  
Sleep Homeostasis ◽  
Chronic Lead Exposure

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep–wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep–wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep–wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

scholarly journals The Tibetan medicineZuotaiinfluences clock gene expression in the liver of mice

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1632 ◽  
Author(s):  
Huan Li ◽  
Wen-Kai Li ◽  
Yuan-Fu Lu ◽  
Li-Xin Wei ◽  
Jie Liu
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Nuclear Receptor ◽  
Clock Gene ◽  
Target Genes ◽  
Oscillation Amplitude ◽  
Biological Clock ◽  
Tibetan Medicine ◽  
Pcr Analysis ◽  
Clock Gene Expression

Background.The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and “detoxification,” and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice.Materials and methods.Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression.Results.Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1–3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα.Conclusion.The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.

scholarly journals The core clock genePer1phases molecular and electrical circadian rhythms in SCN neurons

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2297 ◽  
Author(s):  
Jeff R. Jones ◽  
Douglas G. McMahon
Keyword(s):  
Gene Expression ◽  
Firing Rate ◽  
Clock Gene ◽  
Biological Clock ◽  
Synaptic Activity ◽  
Spontaneous Firing ◽  
Transgenic Mouse Line ◽  
The Core ◽  
Clock Gene Expression ◽  
Spontaneous Firing Rate

The brain’s biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used aPer1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAAreceptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock genePer1, but persists in the absence of the core clock genePer2. These results suggest thatPer1plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping.

scholarly journals Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome

2020 ◽  
Author(s):  
Yi Liu ◽  
Xiuhong Weng ◽  
Shaoling Yu ◽  
Yumei Ding ◽  
Bo Cheng
Keyword(s):  
Gene Expression ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Clock Gene ◽  
Clock Genes ◽  
Biological Clock ◽  
Lymphocyte Infiltration ◽  
Clock Gene Expression ◽  
Melatonin Administration ◽  
Gland Function

Abstract Background Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS. Methods Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry. Results There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice. Conclusion pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS.

scholarly journals Cold-Inducible RNA-binding protein (CIRBP) adjusts clock gene expression and REM sleep recovery following sleep deprivation

2018 ◽  
Author(s):  
Marieke MB Hoekstra ◽  
Yann Emmenegger ◽  
Paul Franken
Keyword(s):  
Gene Expression ◽  
Sleep Deprivation ◽  
Rem Sleep ◽  
Clock Gene ◽  
Rna Binding ◽  
High Amplitude ◽  
Knock Out ◽  
Clock Gene Expression ◽  
Sleep Homeostasis

AbstractSleep depriving mice affects clock gene expression, suggesting that these genes partake in sleep homeostasis. The mechanisms linking wakefulness to clock gene expression are, however, not well understood. We propose CIRBP because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation (SD) induced changes in clock gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the SD-incurred changes in cortical expression of the clock gene Rev-erbα whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied by an acceleration of theta oscillations. Thus, CIRBP adjusts cortical clock gene expression after SD and expedites REM sleep recovery.

scholarly journals Cold-inducible RNA-binding protein (CIRBP) adjusts clock-gene expression and REM-sleep recovery following sleep deprivation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Marieke MB Hoekstra ◽  
Yann Emmenegger ◽  
Jeffrey Hubbard ◽  
Paul Franken
Keyword(s):  
Gene Expression ◽  
Sleep Deprivation ◽  
Rem Sleep ◽  
Clock Gene ◽  
Rna Binding ◽  
High Amplitude ◽  
Knock Out ◽  
Clock Gene Expression ◽  
Sleep Homeostasis

Sleep depriving mice affects clock-gene expression, suggesting that these genes contribute to sleep homeostasis. The mechanisms linking extended wakefulness to clock-gene expression are, however, not well understood. We propose CIRBP to play a role because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock-gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation-induced changes in clock-gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the sleep-deprivation incurred changes in cortical expression of Nr1d1, whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied with faster theta oscillations compared to WT mice. Thus, CIRBP adjusts cortical clock-gene expression after sleep deprivation and expedites REM-sleep recovery.

Daily rhythm and regulation of clock gene expression in the rat pineal gland

2004 ◽  
Vol 120 (2) ◽  
pp. 164-172 ◽  
Author(s):  
V Simonneaux ◽  
V.-J Poirel ◽  
M.-L Garidou ◽  
D Nguyen ◽  
E Diaz-Rodriguez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pineal Gland ◽  
Clock Gene ◽  
Daily Rhythm ◽  
Clock Gene Expression ◽  
Rat Pineal Gland

A genetic CLOCK variant associated with cluster headache causing increased mRNA levels

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 496-502 ◽  
Author(s):  
Carmen Fourier ◽  
Caroline Ran ◽  
Margret Zinnegger ◽  
Anne-Sofie Johansson ◽  
Christina Sjöstrand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythm ◽  
Cluster Headache ◽  
Clock Gene ◽  
Control Sample ◽  
Mrna Levels ◽  
Nucleotide Polymorphisms ◽  
Primary Fibroblast ◽  
Clock Gene Expression ◽  
Diurnal Preference

Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene encodes a transcription factor that serves as a basic driving force for circadian rhythm in humans and is therefore particularly interesting as a candidate gene for cluster headache. Methods We performed an association study on a large Swedish cluster headache case-control sample (449 patients and 677 controls) screening for three single nucleotide polymorphisms (SNPs) in the CLOCK gene implicated in diurnal preference (rs1801260) or sleep duration (rs11932595 and rs12649507), respectively. We further wanted to investigate the effect of identified associated SNPs on CLOCK gene expression. Results We found a significant association with rs12649507 and cluster headache ( p = 0.0069) and this data was strengthened when stratifying for reported diurnal rhythmicity of attacks ( p = 0.0009). We investigated the effect of rs12649507 on CLOCK gene expression in human primary fibroblast cultures and identified a significant increase in CLOCK mRNA expression ( p = 0.0232). Conclusions Our results strengthen the hypothesis of the involvement of circadian rhythm in cluster headache.

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